Linaclotide (Linzess): effects, uses and side effects
Clinical review pending
How linaclotide works for constipation and irritable bowel syndrome with constipation, which US-approved populations are listed, and its side effects and contraindications.
Linaclotide is used for certain forms of chronic constipation and irritable bowel syndrome with constipation. The medicine increases the amount of fluid entering the intestine. This softens stool and helps it move through the bowel faster. In irritable bowel syndrome, linaclotide can also relieve abdominal pain. Diarrhea is an important side effect: when severe, it can cause the body to lose too much fluid.
What is linaclotide?
Linaclotide is available under the brand name Linzess and, in some regions, Constella. It consists of a chain of 14 amino acids, making it a peptide. It is taken by mouth but barely enters the bloodstream, acting almost entirely within the gut.
Its uses include chronic constipation and irritable bowel syndrome with constipation, abbreviated IBS-C. In these conditions, intestinal contents can move more slowly than usual, and abdominal discomfort can occur. Linaclotide was developed as MD-1100 and approved in the United States in 2012.
How does linaclotide work?
Linaclotide activates a receptor called guanylate cyclase C on the cells lining the intestine. This raises concentrations of the signaling molecule cyclic GMP inside and outside these cells. Through this pathway, channels for chloride and bicarbonate open, and the cells release more fluid into the intestine. Stool becomes softer and passes through the bowel faster, relieving constipation.
Outside the cells, cyclic GMP may also reduce the sensitivity of pain-signaling nerves in the intestinal wall. This could explain why abdominal pain decreased with linaclotide in IBS-C. The medicine stays largely in the gut; very little is absorbed into the body.
In the phase 3 IBS-C trial program, approximately one-third of people treated with linaclotide responded according to the FDA’s combined assessment criteria. The figure with placebo was about 14%. These figures do not mean that those people were cured or symptom-free. 1
Is linaclotide FDA-approved?
Yes. The US Food and Drug Administration initially approved linaclotide for adults and later for children. Indications differ by age group. 2
| Indication | Population | FDA approval |
|---|---|---|
| Irritable bowel syndrome with constipation (IBS-C) | Adults | 2012 |
| Chronic idiopathic constipation | Adults | 2012 |
| Irritable bowel syndrome with constipation (IBS-C) | Children aged 7 and older | Later approval |
| Functional constipation | Children aged 2 and older | Later approval |
Use in children under 2 is prohibited. US prescribing information highlights this in a boxed warning, a particularly prominent warning. It was prompted by deaths in very young laboratory animals caused by severe dehydration, or fluid loss.
What is linaclotide prescribed for?
The listed US indications include irritable bowel syndrome with constipation in adults and children aged 7 and older, and chronic idiopathic constipation in adults. “Idiopathic” means that no clear cause is known. Functional constipation in children aged 2 and older is also included. Here, this means impaired bowel function for which no organic cause has been identified. US prescribing information, source 2
It is taken once daily on an empty stomach. Children under 2 must not receive linaclotide.
What side effects can occur?
The US prescribing information, source 2, lists the following common side effects:
- Diarrhea, also the most frequent reason for stopping treatment
- Abdominal pain
- Increased intestinal gas and abdominal bloating
Severe diarrhea can cause dehydration and is therefore among the more serious risks.
Linaclotide must not be used in children under 2; this is the subject of the prominent boxed warning in US prescribing information. Known or suspected intestinal obstruction also rules out its use.